1. Field of the Invention
Desmethylimipramine (a dibenzazepine derivative also referred to as desipramine) finds extensive use for the treatment of depression. In administering desmethylimipramine, it is frequently necessary to ensure that the desmethylimipramine blood level remains within a certain narrow concentration range, in order to insure effective dosage, while avoiding levels which may be toxic or produce undesirable effects.
It is desirable to provide a simple and rapid procedure for determining desmethylimipramine levels in serum or other physiological fluids, which provides reproducible values and is specific for the compound(s) of interest.
2. Brief Description of the Prior Art
Desmethylimipramine is closely related chemically to imipramine, amitriptyline and nortriptyline. Techniques reported for the determination of amitriptyline in biological fluids include the use of thin layer chromatography, gas-liquid chromatography (GLC) and GLC-mass spectrometry. Gilford, et al., J. of Chrom., 105, 107-113 (1975); Gupta, et al., Clin. Biochem., 9, 3 247-51 (1976); Nyberg and Martensson, J. Chrom., 143, 491 (1977); Watson and Steward, J. Chrom., 134, 182 (1977); ibid, 132, 155-159 (1977). Radioimmunoassay has been reported for amitriptyline by Aherne, et al., Br. J. Clin. Pharmac., 3, 561 (1976); Turner, Lancet, 1316 (1977); and Aherne et al., Lancet, 1214 (1977). In Aherne, et al., ibid, a synthesis for an antigen for antibody formation is described, where nortriptyline is substituted with aminobutylene followed by conjugation to bovine serum albumin employing carbodiimide. In another antigen conjugate synthesis by Kaul, et al., J. Anal. Tox., 1, 236 (1977), nortriptyline was conjugated to bovine serum albumin through a succinic group. The resulting antibodies were found to have significant cross-reactivity with a number of other tricyclic drugs.
U.S. Pat. No. 4,275,160 discloses imipramine derivatives and poly(amino acid) conjugates. U.S. Pat. No. 4,307,245 describes amitriptyline conjugates to antigenic proteins and enzymes. U.S. Pat. No. 4,220,722 discloses a method for conjugating to polyamino compounds employing haloacyl groups and compositions prepared thereby.